Intrathecal antibody production against Epstein-Barr and other neurotropic viruses in pediatric and adult onset multiple sclerosis.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of multiple sclerosis (MS). Recent reports proposed an increased EBV-targeted humoral immune response in MS, which appears to be more pronounced in pediatric patients. However, little is known about the CNS-derived antibody production against EBV in patients with MS.

Early reduction of total N-acetyl-aspartate-compounds in patients with classical vanishing white matter disease. A long-term follow-up MRS study.

The neuropathology of vanishing white matter (VWM) disease is characterized by a loss of white matter (WM). Although recent histopathological studies suggest a primary glial dysfunction, the purpose of this work was to assess the extent of axonal involvement in VWM using long-term follow-up proton MR spectroscopy. White and gray matter of nine children with genetically proven VWM and late infancy/early childhood onset were investigated with short-echo time, single-voxel proton MR spectroscopy over up to 8 years starting as early as less than 2 years after the onset of symptoms (5 patients).

Common infectious agents in multiple sclerosis: a case-control study in children.

Environmental factors, in particular infections, have been linked with the risk of developing multiple sclerosis (MS). The association of Epstein-Barr virus infection with childhood onset of MS has been recently recognized. As other infections characteristically experienced during childhood have not yet been studied in larger cohorts of paediatric MS, we conducted a study on 152 German children with MS (age at onset <16 years) and matched controls in the hope of gaining evidence for their possible aetiological role in MS.

Pediatric multiple sclerosis: a short history of a long story.

Shortly after multiple sclerosis (MS) was described by Charcot in 1872-1873, symptoms of MS were noted in children. At the time of these observations (late 19th century), the many inherited demyelinating diseases that manifest during childhood had not yet been recognized. Once the inherited demyelinating disorders became known, MS as a childhood disease was dismissed as a possible diagnosis.

Valproic acid-induced pancreatitis: 16 new cases and a review of the literature.

Background: Acute pancreatitis is rarely seen in children, and, in contrast to cases in adults, it is often drug induced. One possible medication is the antiepileptic drug valproic acid (VPA), which is commonly prescribed for generalized and focal epilepsy, migraine, neuropathic pain, and bipolar disorder. The common side effects associated with VPA are typically benign, but less common but more serious adverse effects may occur.

Virchow-Robin spaces on magnetic resonance images of children with adrenoleukodystrophy.

Background: Perivascular spaces of the brain, also known as Virchow-Robin spaces (VRS), are of immunological and neuropathological relevance and can be observed in magnetic resonance images (MRI). Their histopathological significance in X-linked adrenoleukodystrophy (ALD) has been reported. Aim of this study was to elucidate the prognostic or diagnostic value of VRS on MRI of the brain in the evaluation of onset or severity of the clinical course in ALD.

Paediatric multiple sclerosis and acute disseminated encephalomyelitis in Germany: results of a nationwide survey.

Unlabelled: The aim of this study was to evaluate the incidence of paediatric multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) in Germany. In a prospective nationwide survey carried out between 1997 and 1999, all registered new cases of paediatric MS and ADEM with an onset before the age of 16 years were evaluated using a standardised questionnaire. A total of 132 patients with suspected or definite MS and 28 patients with an assumed diagnosis of ADEM were reported.

Quantitative proton MRS of cerebral metabolites in laminin alpha2 chain deficiency.

Congenital muscular dystrophy (CMD) due to merosin (laminin alpha2 chain) deficiency is an autosomal recessively inherited disorder characterized by severe muscular weakness and hypotonia from birth on. Brain involvement is the rule and characterized by variable T2 hyperintensities of white matter which appears swollen on cranial MRI. The pathophysiology of these white matter changes is not clear.

Recurrent optic neuritis associated with Chlamydia pneumoniae infection of the central nervous system.

It has been suggested that Chlamydia pneumoniae (C. pneumoniae) is involved in the pathogenesis of diverse diseases of the central nervous system (CNS), including multiple sclerosis. We report the case of a 12-year-old male with isolated recurrent optic neuritis and an associated CNS infection with C.

Virchow-Robin spaces on magnetic resonance images: normative data, their dilatation, and a review of the literature.

Introduction: Virchow-Robin spaces (VRS) are perivascular spaces in the brain and can be visualized on magnetic resonance images (MRI). We attempt to provide a better understanding of the significance of VRS for pathological and physiological processes by reviewing the literature, presenting normative data for the first time, and proposing a definition for the dilatation of the VRS on MRI that is based on shape rather than size.

Methods: We evaluated the VRS in 125 healthy subjects (age range 1-30 years) using high-resolution 3D images, and in 36 patients (age range 2-16 years) with normal MRI, using routine clinical sequences.

Pediatric multiple sclerosis: detection of clinically silent lesions by multimodal evoked potentials.

Pediatric patients with multiple sclerosis (MS) frequently do not meet MRI criteria for diagnosis because of lack of evidence of dissemination in space. We assessed the diagnostic utility of multimodal evoked potentials (EP). In 46% of 85 childhood patients with MS, spatial dissemination was detected by EP before the second clinical attack.

Magnetic resonance imaging and proton magnetic resonance spectroscopy of megalencephaly and dilated Virchow-Robin spaces.

Megalencephaly with dilated Virchow-Robin spaces has been suggested to represent a new clinical entity. This report describes two males and a female who have been monitored from pregnancy. The patients manifest a relatively normal psychomotor development with some minor neurologic symptoms such as mild muscle hypotonia and clumsy motor performance.

X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene.

We previously reported two unrelated boys aged 3 and 8 years with mutations in the thyroid hormone transporter gene MCT8 resulting in severe global retardation and an uncommon pattern of thyroid hormone abnormalities. We now further describe an unusual neurological phenotype associated with these mutations, namely paroxysmal kinesigenic dyskinesias (PKD), provoked by certain stimuli including changing of their clothes or diapers. It is not clear how the MCT8 defect causes PKDs.

Identification of ten novel mutations in patients with eIF2B-related disorders.

Autosomal recessive inherited mutations in each of the five eukaryotic initiation factor 2B (eIF2B) subunits are known to cause white matter abnormalities with a wide continuum of clinical signs and severity leading to the concept of eIF2B-related disorders. The clinical spectrum extends from fatal infantile forms to adult forms with slow or absent neurological deterioration. In this study 15 well-characterised patients with the classical form of leukoencephalopathy with vanishing white matter (VWM) or with phenotypic variants like ovarioleukodystrophy were investigated for mutations in the genes EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5 encoding eIF2B.

Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a.

The authors studied the tolerability of subcutaneous interferon beta-1a (IFNbeta-1a) in 51 patients with early-onset multiple sclerosis. The most frequent systemic adverse effects were flu-like symptoms in 65%. Laboratory abnormalities included asymptomatic leukopenia (27%) and elevated hepatic transaminases (35%).

Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes.

Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in the three genes coding for the alpha chains of collagen VI and characterized by generalized muscle weakness, striking hypermobility of distal joints in conjunction with variable contractures of more proximal joints, and normal intellectual development. The diagnosis is supported by abnormal immunoreactivity for collagen VI on muscle biopsies. As patients with UCMD show clinical characteristics typical of classical disorders of connective tissue such as Ehlers-Danlos syndromes (EDS), we investigated the ultrastructure of skin biopsy samples from patients with UCMD (n=5).

Monocyte/macrophage differentiation in dermatomyositis and polymyositis.

Recent advances have revealed significant differences in the pathogenesis of inflammatory myopathies. To determine whether different patterns of macrophage differentiation are a useful tool to delineate the major groups of inflammatory myopathies, the muscle biopsies of 11 patients with dermatomyositis and 12 patients with polymyositis were studied using different macrophage markers. In polymyositis, the early-activation markers MRP14 and 27E10 stained the majority of macrophages, which were recognized by the pan-macrophage marker Ki-M1P and which were located primarily in the endomysium.

Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene.

Desmin-related myopathies (DRMs) are a heterogeneous group of muscle disorders, morphologically defined by intrasarcoplasmic aggregates of desmin. Mutations in the desmin and the alpha-B crystallin genes account for approximately one third of the DRM cases. The genetic basis of the other forms remain unknown, including the early-onset, recessive form with Mallory body-like inclusions (MB-DRMs), first described in five related German patients.

Actin-related myopathy without any missense mutation in the ACTA1 gene.

Actinopathies are defined by missense mutations in the ACTA1 gene coding for sarcomeric actin, of which some 70 families have, so far, been identified. Often, but not always, muscle fibers carry large patches of actin filaments. Many such patients also have nemaline myopathy, qualifying actinopathies as a subgroup of nemaline myopathies.

Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anaemia: case report and review of the literature.

Unlabelled: Vitamin B(12) deficiency is one of the major causes of megaloblastic anaemia with or without neurological symptoms. We report on a patient manifesting acute encephalopathy, epilepsy, microcephaly and megaloblastic anaemia at the age of 4 months. Vitamin B(12) deficiency in the patient was due to subclinical pernicious anaemia of the mother who exhibited neither haematological nor neurological symptoms.

Progressive muscle weakness after high-dose steroids in two children with CIDP.

Corticosteroids and intravenous immunoglobulins belong to the first line of treatment in chronic inflammatory demyelinating polyneuropathy. In patients with a progressive course, plasma exchange and immunomodulatory drugs are added to the regimen. To reduce the side effects of long-term oral prednisolone, high-dose pulsatile intravenous methylprednisolone treatment has been advocated.